Differentiation

The human visual system notices misalignment and variations
in patterns.

Typographic contrast needs to be sufficient so that it's
not perceived as a mistake, but the more contrast you use,
the more important the difference will seem.
Professional typeface designers are trained in this.

Therefore, use italics for emphasis, and avoid changing
both type size and weight at the
same time (e.g. for
sub-headings).